Abstract
Serotonin reuptake inhibitors and cognitive-behavior therapy (CBT) are considered first-line treatments for obsessive-compulsive disorder (OCD). However, little is known about their modulatory effects on regional brain morphology in OCD patients. We sought to document structural brain abnormalities in treatment-naive OCD patients and to determine the effects of pharmacological and cognitive-behavioral treatments on regional brain volumes. Treatment-naive patients with OCD (n=38) underwent structural magnetic resonance imaging scan before and after a 12-week randomized clinical trial with either fluoxetine or group CBT. Matched-healthy controls (n=36) were also scanned at baseline. Voxel-based morphometry was used to compare regional gray matter (GM) volumes of regions of interest (ROIs) placed in the orbitofrontal, anterior cingulate and temporolimbic cortices, striatum, and thalamus. Treatment-naive OCD patients presented smaller GM volume in the left putamen, bilateral medial orbitofrontal, and left anterior cingulate cortices than did controls (p<0.05, corrected for multiple comparisons). After treatment with either fluoxetine or CBT (n=26), GM volume abnormalities in the left putamen were no longer detectable relative to controls. ROI-based within-group comparisons revealed that GM volume in the left putamen significantly increased (p<0.012) in fluoxetine-treated patients (n=13), whereas no significant GM volume changes were observed in CBT-treated patients (n=13). This study supports the involvement of orbitofronto/cingulo-striatal loops in the pathophysiology of OCD and suggests that fluoxetine and CBT may have distinct neurobiological mechanisms of action.
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Acknowledgements
We thank Dr Cristina Belotto-Silva, Ms Sonia Borcatto, Dr Ana Gabriela Hounie, Ms Marines Alves Joaquim, Ms Ana Carolina Ferreira Rosa, and Ms Luciana Cristina Santos whose help was critical to the conduction of this project. We also thank Ms Dianne M Hezel for helpful comments on the manuscript. This study received financial support in the form of grants provided by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Foundation for the Support of Research in the State of São Paulo) to Dr Miguel (2005/55628-8) and from FAPESP scholarships to Dr Shavitt (06/61459-7), to Dr Diniz (06/50273-0), to Dr Lopes (2008/10257-0), and to Ms D’Alcante (06/58286-3). Dr Hoexter is supported by a PhD scholarship from FAPESP (2005/04206-6) and by a doctorate ‘sandwich’ scholarship from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Agency for Support and Evaluation of Graduate Education) (4375/08-4). This work was presented in part at the 48th Annual Meeting of the American College of Neuropsychopharmacology, 6–10 December 2009, Hollywood, Florida, USA.
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Dr Hoexter, Dr Duran, Ms D’Alcante, Dr Shavitt, Dr Lopes, Dr Diniz, Mr Batistuzzo, and Dr Busatto have declared no conflict of interest. Dr Dougherty has acted as a consultant for Medtronic, Eli Lilly, Brand Ideas, McNeil, and Reed Elsevier, and has received research funding from Medtronic, Eli Lilly, McNeil, and Cyberonics. Dr Deckersbach's research has been funded by NIMH, NARSAD, TSA, OCF, and Tufts University. He has received honoraria, consultation fees, and/or royalties from the MGH Psychiatry Academy, BrainCells, Systems Research and Applications Corporation, Boston University, the Catalan Agency for Health Technology Assessment and Research, the National Association of Social Workers Massachusetts, the Massachusetts Medical Society, Tufts University, NIDA, German Research Foundation/Federal Ministry for Education and Research, and Oxford University Press. He has also participated in research funded by NIH, NIA, AHRQ, Janssen Pharmaceuticals, The Forest Research Institute, Shire Development, Medtronic, Cyberonics, and Northstar. Dr Bressan has received honoraria and/or consultations fees from Novartis, Eli Lilly, Janssen, and AstraZeneca. Dr Miguel has received lecture fees from Lundbeck and Solvay.
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Hoexter, M., de Souza Duran, F., D'Alcante, C. et al. Gray Matter Volumes in Obsessive-Compulsive Disorder Before and After Fluoxetine or Cognitive-Behavior Therapy: A Randomized Clinical Trial. Neuropsychopharmacol 37, 734–745 (2012). https://doi.org/10.1038/npp.2011.250
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